Book of Abstracts: Albany 2009

Watson-Crick Recognition of Double-Stranded B-DNA

Nature has settled on double helical DNA as the storehouse of genetic information because of its ability to protect the genetic codes from reactive chemical species. While this strategy may confer evolutionary advantage to organisms by preserving the integrity and safe transfer of their genetic information, it presents a major challenge for chemists and biologists trying to develop means to recognize this natural biopolymer. Pursuit of this goal has in the past generally been focused on the minor and major groove because of their ease of accessibility. Now we show that sequence-specific recognition of double helical B-form DNA (B-DNA) can be established through direct Watson-Crick base-pairing by using conformationally-preorganized γ-peptide nucleic acids (γ-PNAs). Binding occurs in a highly sequence-specific manner through a strand-invasion mechanism. Unlike other approaches that have been developed to date, only a single strand of γ-PNA is required for binding and it can be applied to any sequence or target length.